The overall objectives of this research is to gain a better understanding of the genetic controls of normal and abnormal development of the mammalian central nervous system. To do this we will use mice with inherited genetic defects of the brain and retina. The mutants to be studied are expressed either early postnatally or in the embryo. One of our prime goals will be to determine in which cell type(s) a particular mutant gene acts. To do this we will produce experimental mouse chimeras. These chimeras will contain mixtures of genetically normal and mutant cells. With independent cell markers we will determine the genotype of cells regardless of their phenotype. In this way, we can sort out in which cell type the mutant gene is acting. The mutants and chimeras will be examined by histological, histochemical and electron microscopic techniques. The chimeras will also be used to study neuronal migration and mosaic patterns in the developing nervous system.